Novel skin care compositions

ABSTRACT

Skin care compositions are provided comprising a highly hydrophobic substance, an alkaryl polyfluorocarbon, particularly a substituted phenyl-polyfluoroacylamino propanamide, an alkanol and refined oils and the oil triglyceride fractions in sufficient amount to provide substantial homogeneity. When employed for hirsutism, optionally antioxidants and moisturizer are added. For use against wrinkles, additionally vitamins, antioxidants and a mixture of extracts of naturally occurring substances are present.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional PatentApplication No. 60/713,882 filed on Sep. 1, 2005, which is herebyincorporated by reference in its entirety.

STATEMENT OF GOVERNMENTAL SUPPORT

This invention was not made with Government Support.

REFERENCE TO SEQUENCE LISTING, COMPUTER PROGRAM, OR COMPACT DISK

None.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The field of this invention concerns cosmetic compositions, particularlyskin care related to skin hormonal imbalance.

2. Related Art

BACKGROUND

Mammalian skin and associated characteristics, such as wrinkles and hairgrowth and loss, are significantly affected by hormones, and theindividual skin responsiveness to their levels and ratios, since thereis substantial interest in the treatment of skin and its associatedcharacteristics, there have been numerous reports of treatment aspalliatives and cures.

1. Wrinkle Reduction:

Wrinkles are skin folds and creases caused by dermal thinning and lossof elasticity, which is a result of the aging process and/or exposure tonoxious substances and/or physical factors such as UV radiation, all ofwhich adversely affect the skin metabolism. Wrinkles are not a medicalcondition and as long as the substances employed to treat them are notsystemically resorbed and systemically active, the preparations fallinto the field of cosmetics.

There are many claims to inventions for non-surgical wrinkle reductionor removal, but there are few systematic studies to support such claims.There is a plethora of facial creams available containing a variety ofsubstances, many of which are either inefficient or induce side effectsat the levels of efficacy. Thus, it is known that topical vitamin C,tretinoin, or isotretinoin, while transiently improving the wrinklescaused by aging and photo damage, have a considerable incidence ofirritation. Inducing paresis of the muscle fibers for cosmetic purposesby substances blocking the neuromuscular junctions is notphysiologically acceptable and has its own particular toxicity.

Topical and/or systemic application of estrogens of human origin havebeen shown to increase the skin collagen content and thus increase skinthickness as well as the concentration of skin mucopolysaccharides,which directly reduces the wrinkles' depth. However, giving mammalianestrogens systemically for the sole purpose of reducing the signs ofskin aging would not be medically defensible. Dermatologists haveexplored topical estriol and 17-β-estradiol and found reduction in thewrinkle depth and increased hydration, but also, albeit to a degree, asystemic resorption resulting in a rise in prolactin (Schmidt et al.,1996 Int J Dermatol 35(9):669-74). Therefore, topical mammalianestrogens for skin regeneration, although effective, cannot qualify as acosmetic preparation and are not authorized in cosmetic creams. Certainphytoestrogens, especially the isoflavones, which are found in a varietyof plants, as are the flavonoids, were shown to have a much lower effectthan the mammal estrogens. However, in a topical application they arenot resorbed systemically (Bayerl and Keil, 2002 Akt Dermatol 28:14-8).

There are many combinations of different ingredients in cosmetics, suchas antioxidants, enzymes, phytoestrogens, emollients, humectants, andthe like. Their ability to protect the skin and reduce the formation ofwrinkles varies with the composition and its ingredients.

There is, therefore, a need for a safe, effective cosmetic that reduceswrinkling, has minimal or no side effects, such as erythema, edema orirritation, is not systemically resorbed when applied to the skin anddoes not result in a change in the skin coloration, e.g., issubstantially transparent when applied.

2. Compositions Affecting, Female Facial Hair Growth (IdiopathicHirsutism):

Approximately eight percent of women are affected by idiopathichirsutism (IH), i.e., excessive male-like pattern hair growth withoutunderlying systemic endocrine pathology. IH is characterized either byhigher sensitivity of the hair follicle androgen receptors to theandrogens or by higher skin androgen levels. IH is considered a skinhyperandrogenetic syndrome in the cosmetic category since especiallydark excessive facial hair is visible and leads to psychologicaldistress.

The current treatment is topical and/or systemic pharmacological,combined with mechanical removal including shaving, depilatories,waxing, plucking, laser, intense pulsed light, and/or electrolysis.Metformin, primarily an antidiabetic treatment, known to be oftenassociated with adverse gastrointestinal effects, is indicated only whenIH is concomitant.

The androgen-targeting drugs improve female IH either by suppression ofthe male hormone synthesis such as by inhibiting 5-α reductaseconversion of testosterone to dihydrotestosterone (by finasteride), orby blocking the androgen receptors. Finasteride and antiandrogens arecontra-indicated in women of childbearing age as they can causefeminization of the male fetus. Cyproterone acetate (CPA), a progestagenwith anti-androgenic properties, carries the risk of hypertension,thromboembolism, diabetes mellitus, hypercholesterolemia and endometrialcancer. An antiandrogen of steroidal structure for topical use wasrecently published (see Labrie et al.). Non-steroidal blocking agents ofthe androgen receptor, such as flutamide or bicalutamide, prevent theandrogen binding. When tested topically in male androgenetic alopeciathey proved to be substantially systemically resorbed; they are notapproved for IH therapy. The antiandrogens, RU 58841 and RU 56187, i.e.,N-substituted aryl hydantoins or thiohydantoins were tested topically;they are nevertheless converted systemically into a common metabolite,which is strongly antiandrogenic. Topical eflornithine inhibitsornithine decarboxylase and thus the conversion of ornithine toputrescine, which regulate the anagen phase of the hair growth.

Mechanical depilation by tweezing and depilatory can potentiallyexacerbate IH by stimulating the growth of thicker and coarser hair,making subsequent treatments more difficult and occasionally inducingfolliculitis and trauma to the hair shaft and skin.

IH can be considered a medical condition, but as long as the substancesemployed to treat IH are not dernally resorbed into the body to becomesystemically active, the preparations fall into the field of cosmetics.A topical cosmetic composition not resorbed systemically, reducing thehair diameter, color and rate of growth and not changing the appearanceof the skin would be of benefit to women affected by unwanted body hair.

Relevant Literature

For wrinkles, the use of natural extracts and their fractions has foundextensive use in cosmetics: resveratrol, WO04/026,222, WO01/30314;Glycine soja, U.S. patent application nos. 2004/0191350, 2005/0048105,2005/0112153; grape seed oil, WO01/17495; Boswellia serrata, U.S. patentapplication no. 2005/01213559 and WO00/0578393; and Cocos nucifera, U.S.Pat. No. 6,551,656. Fluridil has been previously employed informulations useful in a variety of conditions where its effect on theskin receptors is desirable (U.S. Pat. No. 6,184,249, which isspecifically incorporated by reference herein, Sovak et al., 2001 WO01/58854; 2002 Dermatol Surg 28:678-85; Seligson et al., 2003 Drug DevRes 59:292-306).

Relevant Literature

References of interest for treating wrinkles include U.S. Patent Nos.5,889,054, 6,139,829, and 1,180,133. A discussion of hormone replacementis found in Sator et al., 2004 Exp Dermatol 13 Suppl 4:36-40.

For IH, see Goodheart H., “Hirsutism: Pathogenesis and Causes,” Women'sHealth Prim Care 2000, 3:329-37; Azziz R., “The evaluation andmanagement of hirsutism,” Obstet Gynecol 2003, 101:995-1007;Shenenberger D, Utecht L., “Removal of unwanted facial hair,” Am FamPhysician 2002, 66:1907-11; and Dawber RP. “Guidance for the managementof hirsutism,” Current Medical Research and Opinion, 2005,21:1227-1234(8). Also, D. Cousty-Berlin et al., “PreliminaryPharmacokinetics and Metabolism of Novel Non-steroidal Antiandrogens inthe Rat: Relation of their Systemic Activity to the Formation of aCommon Metabolite,” Steroid Biochem Molec Biol 1994, 51:47-55, andLabrie et al., “Topical antiandrogenic steroids,” US 2004/0224935, Nov.11, 2004.

BRIEF SUMMARY OF THE INVENTION

A cosmetic preparation for application to the skin for treatment ofhormone related characteristics employs substituted highly hydrophobicsubstances containing an alkarylpolyfluorocarbon, particularly asubstituted phenyl, perfluoroacylamino- propanamide, with aphysiologically acceptable lower alkanol as a vehicle, in conjunctionwith solubilizing additives, particularly refined vegetable oils andthereof derived triglyceride fractions, associated with the particularcharacteristic being treated. A facial care cosmetic preparation and itsuse for reducing or eliminating the female facial hair in hirsutismoptionally employs a moisturizing agent. A facial care cosmeticpreparation and its use for reducing wrinkles employs, in addition tothe above, a mixture of natural extracts or fractions thereof andoptionally conventional additive(s) particularly antioxidants.

The preparations are substantially transparent non-irritating liquidswhich topically applied are rapidly resorbed into the skin to providefor the reduction of wrinkles and/or hirsutism. The preparations are notappreciably systemically resorbed.

BRIEF DESCRIPTION OF THE DRAWINGS

None.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Facial care cosmetic preparations are provided. These compositionscomprise an effective amount of a highly hydrophobic substancecomprising an alkaryl polyfluorocarbon, particularly a substitutedphenyl, perfluoroacylaminopropanamide, in conjunction with othercomponents providing for auxiliary benefits and solubility, a loweralkanol and at least one refined oil, fraction thereof, and optionallyan antioxidant. (By effective amount is intended a sufficient amount toprovide a therapeutic effect.) The vehicle will comprise a major amountof at least one refined vegetable oil and an oil triglyceride fractionand a minor amount of a physiologically acceptable alkanol of from 2-3carbon atoms. The refined oil and its triglyceridic fractions will bepresent in major amount in the facial cosmetic composition, generally atleast about 50 wt. %, more usually at least about 60 wt. %, and may beup to about 95 wt. %. The refined oil will be vegetable oils such asgrape seed, rapeseed, soybean oils and at least one of oil fractions ofCocos nucifera (C₆₋₁₀ triglycerides) and/or Glycine soja (soybean oil,medium chain triglycerides). For wrinkle reduction, the composition willcomprise at least one, usually a combination, of plant natural extractsor fractions thereof, or synthetic composition equivalents, at least oneantioxidant, but may be a mixture of two or more antioxidants, e.g.,vitamins, and, as appropriate, other additives. For facial hairreduction, the antioxidant will usually be tocopherol and optionally amoisturizing agent will be included.

The preparations are at least substantially homogeneous. They arereadily applied to the skin as a substantially transparent liquid whereit does not cause irritation. The compositions can be used safely,repeatedly. The preparations are not resorbed systemically. The alkarylpolyfluorocarbon compound employed will preferably be a substitutedphenyl, perfluoroacylaminopropanamide. For the most part, the phenylsubstituents will be 4-nitro-3-trifluoromethyl. Compounds of particularinterest are 4-nitro-3-trifluoromethylphenyl substitutedperfluoroacylaminopropanamide, wherein the perfluoroacyl group is offrom 2-3 carbon atoms and said propanamide group is substituted at the2-carbon atom with at least one of hydroxyl and methyl.

Compounds of particular interest are also described in U.S. Pat. Nos.6,184,249 and 6,472,415, referenced above. In particular, thesecompounds comprise substituted phenylalanines comprising of a2-hydroxyl, 2-methylpropionyl and a polyfluoroamido group. Thesecompounds include those of the formula

Wherein:

-   X is nitro (NO₂), cyano (CN), or halogen, preferably F, Cl and Br,    more preferably fluorine and chlorine, most preferably fluorine;-   V is CX₃, where X is halogen preferably F, Cl and Br, more    preferably fluorine and chlorine, and V is most preferably CF₃;-   Z is (CF₂)_(n)CF₃ where n is 0 to 9, preferably 0 to 5, most    preferably 0 to 2. These compounds bind specifically to the androgen    receptor and have activity in blocking hormone receptors, preferably    hormone receptors in the skin (e.g. androgen receptors) diminution    of androgen receptors on the surface of cells and low systemic    resorption when administered topically, while being topically    active.

The compounds may or may not have one or more stereoisomeric centers.The compounds may be used as racemic mixtures or be resolved in theirenantiomers and used as enantiomers.

The subject compounds can be prepared in accordance with conventionalways, varying the particular procedure based on the particular sidegroups. A suitable synthetic method is described in Seligson et al. DrugDev. Res. 59:292-306.

The subject composition for wrinkle reduction employs effective amountsof a variety of physiologically acceptable natural extracts or fractionsthereof, where these compositions have salutary effects for the skinand/or can serve in providing for a substantially uniform composition.Extracts that find application include Japanese knotweed, frankincense,non-saponifiable fractions from vegetable oils such as Brassica olifera(turnip, rape) and Glycine soja fractions, as a supply ofphytoestrogens. In addition, free radical scavengers are used, eithersynthetic or natural, particularly the antioxidant vitamins, Vitamins Aand E.

For hirsutism, moisturizing agents include high molecular weight fattyacid esters of at least about 18 carbon atoms and up to 40 carbon atoms.Various types of moisturizers can be used that fall into a variety ofclasses. Occlusive ingredients include petrolatum, mineral oil,paraffin, squalene, vegetable fats (cocoa butter), animal fats(lanolin), lanolin acid, stearic acid, lanolin alcohol, cetyl alcohol,phospholipids, silicones, etc. Humectants include glycerin, propyleneglycol, urea, sodium lactate, sorbitol, pyrrolidone carboxylic acid,etc. Emollients include octyl dodecanol, hexyl dodecanol, oleyl alcohol,oleyl oleate, octyl stearate, PEG-7, glycerol cocoate, myristylmyristate, isopropyl myristate, stearyl isononanoate, isopropylpalmitate, or isopropyl stearate.

Physiologically acceptable preservatives may also be used in thecompositions, primarily for storage. purposes to inhibit the oxidationof the susceptible ingredients, e.g., BHT, BHA (a mixture of the isomers3-tert-butyl-4-hydroxyanisole and 2-tert-butyl-4-hydroxyanisole), TBHQ(tert-butylhydroquinone), ethoxyquin(6-ethoxy-1,2-dihydro-2,2,4-trimethyl quinoline), propyl gallate (gallicacid, propyl ester), tocopherol, rosemary extract, etc.

To varying degrees, other substances having substantially the sameproperties for the purpose of these compositions may be substituted forthe specific compositions employed. These components will be used in aneffective amount to provide the skin improvement and particularly thereduction in wrinkles or any hair except scalp hair.

The following table indicates the categories of material and the rangesin the skin care reducing composition. TABLE 1 Broad Range Narrow RangeComponent parts by weight Parts by weight phenyl- 0.5-5 1-4polyfluoroalkylamidopropanamide e.g., 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2- trifluoroacetylamino) propanamide(fluridil) Natural extracts 0.5-5 0.75-3   Japanese knotweed(resveratrol) 0.1-2 0.2-1   Boswellia serrata (60-70% triterpenes) 0.1-20.2-1   Brassica oleifera and/or Glycine soja 0.1-2 0.2-1  (unsaponifiable fractions, phytoestrogens) Refined oils   50-95 60-95Grape seed oil (refined)   25-60 30-50 Cocos nucifera oil, medium chain  30-65 35-60 triglyceride fractions (refined) Antioxidants   2-10 3-7Vitamin A 0.5-4 0.5-2   Vitamin E   1-5 2-5 Organic polar solvent 2.5-10   3-7.5 (e.g., rubbing alcohol) Preservatives   0-0.5 0.05-0.2 

The following table indicates the categories of material and the rangesin the hirsutism reducing composition. TABLE 2 Broad Range Narrow RangeComponent parts by weight Parts by weight phenyl- 0.5-5   1-4polyfluoroalkylamidopropanamide e.g., 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2- trifluoroacetylamino)propanamide(fluridil) Refined oils 80-95 85-95 Glycine soja (refined) 25-60 30-50Cocos nucifera oil, medium chain 30-65 35-60 triglyceride fractions(refined) Moisturizer 0-2   0-1.5 Antioxidants 1-7 2-6 Vitamin E 1-5 2-5Organic polar solvent (e.g., rubbing 2.5-1     3-7.5 alcohol)Preservatives   0-0.5 0.05-0.2 

The subject compositions can be prepared using various protocols andorders of addition. For the wrinkle reduction compositions,conveniently, a first mixture (A) is prepared in the polar solventheated to a range of about 50 to 80° C., preferably 60° C. to which thenatural extract components is added sequentially and stirred untildissolved, e.g., resveratrol followed by the Olibanum extract. Themixture is stirred until completely homogenous and set aside. To thestirred Cocos nucifera oil triglyceride fraction (refined) at a mildlyelevated temperature, generally in the range of about 35-50° C., isadded the phenyl-perfluoroacylaminopropanamide and the mixture agitatedfor sufficient time to provide homogeneity, usually 20 minutes isadequate. To this mixture is then added the vegetable oil and theantioxidant preservative, followed by the vitamins. After stirring untilthe mixture appears homogeneous, the previously prepared mixture (A) isadded dropwise with agitation to provide a concentrate that can bestored at below room temperature in a dark container.

For the hirsutism compositions, the phenyl-perfluoroacylaminopropanamideis added to the polar solvent and the mixture agitated for sufficienttime to provide homogeneity, usually about 20 minutes. To this mixtureare then added the vegetable oils and their triglyceride fractions, asappropriate, the antioxidant preservative, followed optionally by theantioxidant, e.g., tocopherol. If a moisturizing agent is desired, it isadded slowly, e.g., dropwise, with agitation to provide a final mixturethat can be stored at below room temperature in a dark container.

Various precursor compositions can be prepared having fewer than all ofthe components and the components added subsequently.

As distinct from other formulations, the subject formulations areusually at least substantially free of hydroxyacids and in the case ofthe wrinkle composition also free of monocarboxylic acid esters findinguse in other cosmetic compositions.

Either the extracts or fractions thereof or the known activeingredient(s) may be used. Because of the economics, usually it will bepreferred to use the natural extracts as the source of the activeingredient(s), rather than a substantially pure form, either obtainedfrom a natural source or synthetic. The form of the extract used, whenthe active ingredient is known, will have at least about 50 wt. % of theactive ingredient, and may have 70 wt. % or more. The equivalentcomposition obtained from a different source will have at least about50%, usually at least about 70%, of the individual or mixture of themajor component(s) of the natural extract or fraction thereof.

The phenyl-polyfluoroacylaminopropanamides are described in U.S. Pat.No. 6,184,249. The active compounds that may be employed are substances,which affect the skin androgen receptors but are not appreciablyresorbed systemically. Such compounds are exemplified by2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2-trifluoroacetylamino) propanamide(fluridil).

In the case of Japanese knotweed extract, the extract will usually haveat least about 90% of trans-resveratrol (CAS No.: [501-36-0],3,4′,5-trihydroxy-trans-stilbene, as a glycon (Piceid). Any other sourceof resveratrol may be used that provides at least a substantiallyequivalent amount of resveratrol. Synthetically prepared resveratrol isalso acceptable.

The extract from frankincense, Boswellia serrata, is a terpenoid mixturehaving from about 60-70% of triterpenes, the major portion of which areboswellic acids, of which at least 10 to 30% (wt/wt) is β-boswellicacid, 5 to 20% (wt/wt) is acetyl-β-boswellic acid, 5 to 20% (wt/wt) is11-keto-β-boswellic acid and 5 to 20% (wt/wt) isacetyl-11-keto-β-boswellic acid (CAS No. [8050-07-5]). These extractshave found extensive use as food supplements and in cosmetics asreported in the literature for a wide variety of indications, with manyanecdotal reports of success.

The phytoestrogens are readily available as a fraction derived from thevegetable oils rape- seed (Brassica) and/or soya (Glycine soja). In thesubject formulation, the unsaponifiable fraction (CAS No. [91770-67-1])of the appropriate vegetable oil is used as a source of phytoestrogensand will be substantially free of esters.

The grape seed oil (Vitis vinifera) or the soybean oil is primarily amixture of saturated and unsaturated fatty acids having as its mainconstituents linoleic and oleic acids (>80%). These acids could be usedindependently of the other ingredients or the mixture preparedsynthetically. They are used in their refined form.

Coconut oil (Cocos nucifera) provides primarily medium chaintriglycerides where the acids are primarily C₆₋₁₀ saturated fatty acids,particularly caprylic and capric (CAS [73398-61-5]). It is used in itsrefined form.

Various antioxidants may be used that are conventionally found incosmetic formulations. Vitamins A and E in their commercially availableforms are favored, since they also are known to provide salutaryphysiological effects on the skin, but other antioxidants may also beemployed, such as compounds having phenolic hydroxy functions, ascorbicacid and its derivatives/esters; beta-carotene; catechins; curcumin;ferulic acid derivatives (e.g., ethyl ferulate or sodium ferulate);gallic acid derivatives (e.g., propyl gallate); lycopene; reductic acid;rosmarinic acid; tannic acid; tetrahydrocurcumin; tocopherolderivatives; uric acid; or any mixtures thereof Other suitableantioxidants are those having one or more thiol (—SH) functions, ineither reduced or non-reduced form, such as glutathione, lipoic acid,thioglycolic acid, and other sulfhydryl compounds. The antioxidant maybe inorganic, such as bisulfites, metabisulfites, sulfites, or otherinorganic salts and acids containing sulfur. These antioxidants may beused in partial or complete replacement of the vitamins and theantioxidant preservative, and for the vitamins, usually partial if atall, and will generally be present in less than 50% of the amountindicated for the vitamins, usually less than 30% indicated for thevitamins, generally being present to up to about 2 parts, more usuallynot more than about I part, while for the antioxidant preservative, theymay be used as a complete replacement.

An alkanol is used of from 2-3 carbon atoms, e.g., ethanol, propyleneglycol and isopropanol, particularly the latter in an amount to provideat least substantial homogeneity to the formulation.

Also usually included will be preservatives in minor amount, usually notmore than about 3 different preservatives. The antioxidants describedabove may serve as preservatives. More conventionally BHT, BHA, TBHQ,ethoxyquin, propyl gallate, and rosemary extract is employed.

A particularly important aspect of this invention is the preferredformulation as described in the experimental section. The ingredientcombination is formulated to solubilize all substances in a cosmeticallyacceptable medium. Several components, but particularly the extractsfrom Boswellia serrata, as well as the Japanese knotweed extract, arehighly insoluble in customary systems. The combination forms ahomogenous solution in the subject mixture of medium chain triglycerides(caprylic/capric triglycerides) with fractions of purified grape seedoil and the addition of a minimal amount (less than 10%) of rubbingalcohol (isopropanol).

The resulting mixture is a viscous liquid of oily appearance, whichnevertheless becomes invisible on the skin within a short time after itstopical application: the skin surface is not oily and the overall effectis that of high skin pliability and smoothness.

In addition to the above-enumerated.ingredients, there may be otheradditives that are included for specific purposes. These additives andadjuvants are conventional in the cosmetic, pharmaceutical ordermatological field, such as hydrophilic or lipophilic gelling agents,hydrophilic or lipophilic active agents, solvents, fragrances, fillers,bactericides, odor absorbers and dyestuffs or colorants. The amounts ofthese various additives and adjuvants are those conventionally used inthe field, and, for example, range from 0.01% to 10% of the total weightof the composition.

Emulsifiers that may be used include glyceryl stearate, polysorbate 60,PEG-6/PEG-32/glycol stearate mixture, etc.

Hydrophilic gelling agents include carboxyvinyl polymers (carbomer),acrylic copolymers such as acrylate/alkylacrylate copolymers,polyacrylamides, polysaccharides, such as hydroxypropylcellulose,natural gums and clays, and, as lipophilic gelling agents,representative are the modified clays such as bentones, fatty acid metalsalts such as aluminum stearates and hydrophobic silica, orethylcellulose and polyethylene.

Suitable fatty alcohols and acids include those compounds having from 10to 20 carbon atoms. Especially preferred are such compounds such ascetyl, myristyl, palmitic and stearyl acids and alcohols. Among thepolyols, which may serve as emollients, are linear and branched chainalkyl polyhydroxyl compounds. For example, propylene glycol, sorbitoland glycerin are preferred. Also useful may be polymeric polyols such aspolypropylene glycol and polyethylene glycol. Butylene and propyleneglycol are also useful.

Exemplary hydrocarbons, which may serve as emollients, are those havinghydrocarbon chains anywhere from 12 to 30 carbon atoms. Specificexamples include mineral oil, petroleum jelly, squalene, andisoparaffins.

Another category of functional ingredients within the cosmeticcompositions of the present invention are thickeners. A thickener willusually be present in amounts anywhere from 0.1 to 20% by weight,preferably from about 0.5% to 10% by weight of the composition.Exemplary thickeners are cross-linked polyacrylate materials availableunder the trademark Carbopol. Gums may be employed such as xanthan,carrageenan, gelatin, karaya, pectin and locust beans gum. Under certaincircumstances the thickening function may be accomplished by a materialalso serving as a silicone or emollient. For instance, silicone gums inexcess of 10 centistokes and esters such as glycerol stearate have dualfunctionality.

Powders may be incorporated into the cosmetic composition of theinvention. These powders include chalk, talc, kaolin, starch, smectiteclays, chemically modified magnesium aluminum silicate, organicallymodified montmorillonite clay, hydrated aluminum silicate, fumed silica,aluminum starch octenyl succinate and mixtures thereof.

Other adjunct minor components may also be incorporated into thecosmetic compositions. These ingredients may include coloring agents,opacifiers and perfumes. Amounts of these other adjunct minor componentsmay range anywhere from 0.001% up to 20% by weight of the composition.

The subject compositions will be stored in containers that may beprotected from light, by being opaque to incident light and may besealed to minimize the oxygen present in the empty space. In light ofthe compositions cosmetic nature, the containers will be attractive, mayhave various shapes and come in a variety of sizes. The subjectcompositions may be supplied in conjunction with other skinformulations, as appropriate. The subject preferred compositions arecharacterized as being transparent liquids when applied to the skin.They are not absorbed systemically to any degree that can be found inthe vascular system. They are found to have none to very low acuteirritation potential in standard tests, and are safe for use with humansor other mammals. They have antimicrobial activity against a variety oforganisms, inhibiting the growth of microorganisms in the composition.They have been found to be effective by subjective and objective tests,being described by users as providing a moisturizing and liftingsensation. Mapping and depth measurement of periocular/temporal wrinklesby laser profilometry shows a smoothing effect on the cutaneousmicrorelief, revealed by a decrease in the median depth of microrelieffurrows and a significant decrease in the complexity in a majority ofthe subjects.

With a group of test subjects to provide a p value of less that 0. 1,over about 50 days the volume of the wrinkles as measured by laserprofilometry will be reduced in at least about 60 to 80, more usually atleast about 70% of the subjects, and the depth of the wrinkle is reducedabout 8-15 %, and most usually by at least 10%.

In a clinical study employing the composition of Example 1 (although thecompositions of Examples 8 and 9 would be anticipated to act at least aseffectively), in 9 out of ten facially hirsute women who used in absenceof any other treatment the composition herein described, as 2 mlmassaged once a day into the affected areas, a substantial thinning,loss of color and reduced face and neck hair growth were documented.

The following examples are offered by way of illustration and not by wayof limitation.

EXPERIMENTAL Example 1

A Typical Composition 100 g of the Novel Skin Care Cosmetic Preparation

0.5 g extract from Japanese knotweed (min. 95% trans-resveratrol);3,4′,5-trihydroxy-trans-stilbene, CAS No.: [501-36-0]

0.5 g extract from frankincense (Olibanum)—Boswellia serrata (60-70%triterpenes) CAS No.: [8050-07-5]

0.5 g extract from vegetable oil Brassica oleifera/Glycine soja(unsaponifiable fractions CAS [91770-67-1]

3.0 g vitamin E (DL-α-tocopherol acetate); 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-olacetate, 3.000 IU CAS No.: [7695-91-2]

1.2 g vitamin A (retinol palmitate);3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)2,4,6,8-nonatetraen-1-ol palmitate, 2,000.000 IU, CAS No.: [79-81-2]

2.0 g fluridil CAS No.: [260980-89-0]

0.1 g BHT (butylhydroxytoluene), 2,6-Di-tert-butyl-4-methylphenol CASNo.: [128-37-0]

5.0 g rubbing alcohol (isopropanol), CAS No.: [67-63-0]

40.0 g refined oil from grape seed, CAS No.: [8024-22-4]

47.2 g refined oil (Cocos nucifera) Caprylic/Capric middle chaintriglycerides

Example 2

Ocular Toxicity: Effects on the Ocular Fibroblasts

Rabbit corneal fibroblasts, to which Neutral Red is added in vitro, areexposed to the product at 15, 25 and 50% concentrations for I minute.The cell viability is measured by Optical Density. The culture mediumserves as negative control. IC50 less than 50% was found, indicatingthat the product has a very low toxicity towards ocular mucousmembranes, and is equivalent to the marketed products of the samecategory.

Example 3

Evaluation of the Antimicrobial Properties

The test, according to USP XXV, is based on inoculating the product with5 strains, i.e., S. aureus, P. aeruginosa, E. coli, C. albicans and A.niger, incubation at 20° C. with the counts performed at 7, 14, 21 and28 days. The antimicrobial (“preserving”) efficiency of the product isconsidered positive when at day 14 the bacterial counts (measured byconcentration CFU/g) are reduced by at least 2 logs and in the following14 days continue to drop or stay equal to the starting counts. Foryeasts/moulds the counts must be equal or lower at day 14 and 28,compared to the initial count. TABLE 3 CONCENTRATIONS MEASURED (CFU/g)SOUCHES/STRAINS INOCULUM J7/D7 J14/D14 J21/D21 J28/D28 S. aureus1.90E+07 0.00E+00 0.00E+00 0.00E+00 0.00E+00 P. aeruginosa 2.30E+070.00E+00 0.00E+00 0.00E+00 0.00E+00 E. coli 1.10E+07 0.00E+00 0.00E+000.00E+00 0.00E+00 C. albicans 2.20E+07 0.00E+00 0.00E+00 0.00E+000.00E+00 A. niger 3.10E+07 0.00E+00 0.00E+00 0.00E+00 0.00E+00

The product thus meets the USP XXV criteria as efficiently preservingthe bacterial and fungal sterility.

Example 4

Mutagenicity Determination in vivo

The test is standard to detect possible cytogenetic damage, whichinduces the formation of micronuclei containing lagging chromosomes ortheir fragments. To this end, the preparation was administered topicallyto three dose groups (0.5, 1.5 and 4.5 ml/kg, 5 male and 5 female pergroup) of SKH-1 mice, once daily for 28 days. Peripheral blood wassampled at 36 and 48 hours after the last administration and thereticulocytes were analyzed for the presence or absence of micronucleiafter staining.

No increase in the frequency of micronucleated polychromaticerythrocytes was detected and the product therefore judgednon-mutagenic.

Example 5

48-Hours Single Patch Test in Volunteers

The composition intended for wrinkles was evaluated as an open study on11 adult volunteers, after a single application to the skin in thescapular area, under a semi-occlusive patch for 48 hours. Theobservations aimed at detecting erythema+edema were used to calculatethe acute irritation index (M.I.I.) according to the standard formula torank the cosmetic product according to the scale: M.I.I<0.20Non-irritant (NI); 0.20-M.I.I<0.50 Slightly irritant (SI); 0.50-M.I.I<1Moderately irritant (MI); M.I.I≧1 Irritant (I).

The product was classified as NI, non-irritant.

Example 6

Safety and Efficacy After 28 and 56 Days in Volunteers

On day 0, 28 and 56 in 24 volunteers,

-   -   a. Cutaneous safety was assessed by clinical exam by the        dermatologist aimed at detecting signs of irritation such as        erythema, edema, and urticaria. No significant findings were        reported.    -   b. Laser Profilometry was carried out on a predetermined skin        area and its wrinkles, to determine maximal or average depth,        complexity, volume and isotropy. A precision captor is used,        operating without surface contact to assess the geometric        parameters of the wrinkle and the global skin area microrelief.

The data consists of complexity of the surface (or visual impact of awrinkle in %),—maximum depth of the wrinkle (in mm),—volume of thewrinkle (in mm³) and is analyzed by a paired t-test with significancelimit of p≦0.05.

The findings are summarized in the following table: TABLE 4 % ofvolunteers with Δ% from the Mean ± SEM Δ Student t-test positive effectmean (Day test-Day 0) p significance Complexity Day28 70% −15% −2.7 ±1.2 0.035 Yes (in %) Day56 67% −17% −3.6 ± 2.5 0.164 No Maximum Day2875% −11%  −0.046 ± 03017 0.015 Yes depth of the Day56 72% −11% −0.071 ±0.035 0.061 Limit of wrinkle significance (in mm) Volume Day 28 70% −8%−0.09 ± 0.04 0.031 Yes (in mm³⁾ Day 56 61% −12% −0.20 ± 0.09 0.054 Limitof significance

In conclusion, the product has shown a distinct tendency to reduce thewrinkles after 28 days and after 56 days. The objective findings wereparalleled with the subjective reports of the volunteers.

Example 7

Preparation of 100 g of the Anti-Wrinkle Composition;

To 5.0 g propan-2-ol at 60° C. is added 0.5 g extract of Polygonum(90-95% resveratrol glycon) CAS 501 36 0 and stirred till dissolved,then 0.5 g of the Olibanum extract is added, dissolved and the solutionset aside (sol. A).

To 47.2 g of the coconut oil medium-chain triglyceride fraction at 40°C. is added 2.0 g fluridil (CAS 260980-89-0) and stirred for 20 minutes.0.5 g of the vegetable oil extract (unsaponifiable fraction) and 0.1 gof BHT are added followed by 3.0 g vitamin E and 1.2 g vitamin A. Themixture is stirred until homogenous and sol. A is then added dropwise,under stirring. The resulting solution serves as a stock concentrate,which can conveniently be kept under nitrogen in closed dark containers,at max 15° C.

Final formulation is prepared by addition of 40 g of grape seed oil tothe stock concentrate, to make 100 g of “CARE: the solution for theface” product.

Examples of anti-hirsutism compositions:

Example 8

A Typical 100 g Composition Applicable to Hirsutism*

1.0 g oleyl oleate (octadec-9-enoic acid octadec-9-enyl ester) CAS[3687-45-4]

3.0 g vitamin E (DL-α-tocopherol acetate);3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12trimethyltridecyl)-2H-1-benzopyran-6-ol acetate, 3.000 IU CAS No.:[7695-91-2]

2.0 g fluridil CAS No.: [260980-89-0]

5.0 g rubbing alcohol (isopropanol), CAS No.: [67-63-0]

41.5 g soybean oil, CAS No.: [8001-22-7]

47.5 g refined oil (Cocos nucifera) Caprylic/Capric middle chaintriglycerides

All items other than fluridil are listed in the FDA “InactiveIngredients Database for Approved Drug Products”(http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm).

Example 9

A Typical 100 g Composition of the Cosmetic Oil Applicable to Hirsutism*

2.0 g fluridil CAS No.: [260980-89-0]

6.0 g rubbing alcohol (isopropanol), CAS No.: [67-63-0]

42.0 g soybean oil, CAS No.: [8001-22-7]

50.0 grefined oil (Cocos nucifera) Caprylic/Capric middle chaintriglycerides

All items other than fluridil are listed in the FDA “InactiveIngredients Database for Approved Drug Products”(http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm).

Example 10

Skin Composition Tested in Clinical Hirsutism

Ten females with face hirsutism from 25 to 68 years old were enrolled atthe Department of Dermatology, Palacky University Hospital, Olomouc,Czech Republic. On day 0, photographic documentation of the affectedarea and blood samples were obtained for serum total testosterone andsex hormone binding globulin (SHBG). The subjects were instructed toapply 2 ml of product as a thin layer over the affected area (upper lip,chin, as appropriate) daily, in the evening. On day 90, there were nochanges in the hormonal parameters, and the two dermatologists whoindependently evaluated the images concurred that hair growth,coloration and diameter were substantially reduced in 9 subjects. Therewere no local or systemic side effects.

It is evident from the above results that the subject compositionsprovide for improved skin care. The compositions serve in reducingwrinkles and the ravages of age, sun and toxic substances, includingsmoking, and reduce unwanted facial hair growth. The compositions aresafe, using components that have been shown to be acceptable to humans.Despite using a mixture of hydrophobic and hydrophilic substances, asubstantially homogeneous mixture is obtained that is readily applied tothe skin to provide a transparent layer. The subject compositions can beused repeatedly without irritation to the skin or damage to the skin.

All publications and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it will be readily apparent to those of ordinary skill inthe art in light of the teachings of this invention that certain changesand modifications may be made thereto without departing from the spiritor scope of the appended claims.

1. A skin care composition of cosmetically acceptable components fortopical treatment of wrinkles or hirsutism comprising: an effectiveamount of a physiologically acceptable 4-nitro-3-trifluoromethylphenylsubstituted perfluoroacylaminopropanamide, wherein said perfluoroacylgroup is from 2-3 carbon atoms and said propanamide group is substitutedat the 2-carbon atom with at least one of hydroxyl and methyl; a vehiclecomprising a major amount of at least one naturally occurring refinedoil, a triglyceride oil fraction and sufficient alkanol of from 2-3carbon atoms to provide an at least substantially homogeneous mixture;an effective amount of at least one physiologically acceptableantioxidant; and when said skin composition is for treatment ofhirsutism, said skin composition further optionally comprises amoisturizer; when said skin composition is for wrinkle treatment, saidskin composition further comprises at least one naturally occurringplant extract or fraction thereof.
 2. A composition according to claim1, wherein said composition is for the treatment of wrinkles andcomprises a mixture of at least 3 natural extracts, fractions thereof orcompositional equivalents, selected from the group consisting ofJapanese knotweed, frankincense, an unsaponifiable fraction of Brassicaoleifera and/or Glycine soja.
 3. A composition according to claim 2,wherein refined oil from grape seed and from Cocos nucifera are present.4. A composition according to claim 2, wherein said antioxidants arevitamins.
 5. A composition according to claim 2, wherein said alkanol isisopropanol.
 6. A composition according to claim 1, wherein saidcomposition is for the treatment of hirsutism and comprises refined oilsfrom Glycine soja and Cocos nucifera.
 7. A cosmetic skin composition ofcosmetically acceptable components comprising in parts by weight: 0.5-5parts of2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2-trifluoroacetylamino)propanamide;0.5-5 parts total of natural extracts selected from the group consistingof Japanese knotweed, frankincense, and an unsaponifiable fraction ofBrassica oleifera and/or Glycine soja; 50-95 parts of refined oil fromgrape seed and/or Cocos nucifera; 2-10 parts of antioxidants; and 2.5-10parts of an alkanol of from 2-3 carbon atoms in sufficient amount toprovide a substantially homogeneous mixture.
 8. A composition accordingto claim 7, wherein said antioxidants are Vitamins A and E.
 9. Acomposition according to claim 7, wherein said alkanol is isopropanol.10. A composition according to claim 7, wherein Japanese knotweed andfrankincense are present, and an unsaponifiable fraction of at least oneof Brassica oleifera and Glycine soja.
 11. A cosmetic skin compositionof cosmetically acceptable components comprising in parts by weight: 1-4parts of2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2-trifluoroacetylamino)propanamide;a total of parts 0.75-3 of natural extracts of Japanese knotweed,frankincense, and an unsaponifiable fraction of at least one of Brassicaoleifera and Glycine soja; 30-50 parts of refined grape seed oil; 0.5-2parts of antioxidants; and 3-7.5 parts of an alkanol of from 2-3 carbonatoms in sufficient amount to provide a substantially homogeneousmixture.
 12. A cosmetic skin composition comprising in parts by weight:0.5 parts of2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2-trifluoro-acetylamino)propanamide,0.5 parts of an extract from Japanese knotweed, 0.5 parts of an extractfrom frankincense, 0.5 parts of an unsaponifiable fraction of Brassicaoleifer and/or Glycine soja, 40 parts of refined oil from grape seed,about 47 parts of refined oil fraction from Cocos nucifera, (middlechain-triglycerides) 1.3 parts of Vitamin A, 3 parts of Vitamin E, and 5parts of isopropanol.
 13. A cosmetic skin composition of cosmeticallyacceptable components comprising in parts by weight: 0.5-5 parts of2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-(2,2,2trifluoro-acetylamino)propanamide; at least 80 parts of refined oil fromGlycine soja and/or Cocos nucifera; 2-10 parts of antioxidants; and2.5-10 parts of an alkanol of from 2-3 carbon atoms in sufficient amountto provide a substantially homogeneous mixture.
 14. A compositionaccording to claim 13, wherein said refined oil is present in from 85-95parts, said antioxidant is tocopherol and is present in from 2-6 parts,and a moisturizer is present in an effective amount.
 15. A method ofskin care comprising applying to skin a composition according toclaim
 1. 16. A method of skin care comprising applying to skin acomposition according to claim
 12. 17. A method of skin care comprisingapplying to skin a composition according to claim 13.